2-alkyl-6, 7-dihydro-5-h-thiopyrano (3, 2d) thiazole, quaternaries and process



United StatesPatent 2-ALKYL-6,7-DIHYDRO-5-H-THIOPYRANO (3,2d) THIAZOLE, QUATERNARIES AND PROCESS Robert HQ Sprague, East Hampton, Conn gassignor to Sperry Rand, Corporation, New York, NY, a corporation of Delaware v No Drawing. Original application A ril 27,.1956,Serial s, 1958, SerialNo. 774,798

Claims; or. 260-302 No. 580,996. Dividedandthis applicatio rllioyemher.

2,926,168 Patented Feb. 23, 1960 2 Exrzmpl e. .1..-2.-methyl-6,7-dihydro-5-H-thiopyran0- (3,2d)thiazole- S. 3 av (I; C-CHs.

25.0 g. (1 mol) of 2,4,5,6-tetrahydro-1-thio-3-pyranone (prepared by the method of Fehnel, I. Am. Chem. Soc. 74, 1569 (1952)) was added to a mixture of 38.2 g. (1 mol) of N-bromosuccinimide and 50 ml. of dry carbon tetrachloride. The solution was stirred mechanicallyand after a short time, a vigorous exothermic re actio'ii' occurred. causing refluxing. After the reaction subsided, the mixture was refluxed on the steam bath and cleanly, i.e. without theproductionof excessive fog 51 It is known that cyanine dyes contain-at least two auxochromic nitrogen atoms, the one ternary and the other quaternary, the one nitrogen atom lyingin one heterocyclic nucleus and the other lying in another heterocyclic nucleus, the two nitrogen atoms being connected by a conjugated carbon chain; With'the" thiazole compoundof this invention,- it is possible to prepare cyanine dyes in which one or both of the aforesaid auxo'chromic nitrogen atoms lie in'a 6,7-dihydro-S-H-thiopyrano(3,2d)- thiazole nucleus.

Accordingly, it is the. primary object of the present invention to provide the new: thiazole compound 2-alkyl- 6,7-dihydro-5-H-thiopyrano(3,2d)thiazole.

In accordance with the invention, there is provided for 5 minutes. The. solution waschilled in an ice bath,

the-precipitated s'uccinimide was removed by suction filtrationi an'd' the filtrate was evaporated under reduced,

pressure. The 2'-bromo-2,4,5,6-tetrahydro-l-thio-3-pyranone thusobtainedlwas used'directly in the preparation of the thiazole base. It was mixed with 15.0 g. 1 mol) of thioacetamide and" 100 ml. of absolute ethanol and allowed to'stan'cl' at 0 C. for 3' hours, then overnight at room temperature and finally refluxed for 2 hours;

.The alcohol was distilled ofl andthe viscous brown resii 1 due was diluted with 200 ml. of cold water. The solu-] tion was extracted with 200 ml. of eth'er to removetarry inipurities andtlie'ether extract was washed with 200 m1;

of 5% HCli' The acid washings were combined with the first water solution and made alkaline with dilute the new compound 2 alkyl-6,7-dihydro-S-H-thiopyranm (3,2d-) thiazolehaving the general formulav wherein R represents an alkyl radical C H and N isapositiveinte'ger of from one to three;

Also, in: accordance; with: the inventiong. there ist pro-* vided a process for preparing 2-alkyl-6,7-dihydro 5fi thi0pyrano('3,2d)thiazole comprising reacting 2-bromo- 2,4,5,6-tetrahydro-1-thio-3-pyranone with a thioamide, e.g., thioacetamide or thiopropionamide under heat in an absolute alcohol solution or intheabsence of solvent.

For a better understanding of the invention, together with other and further objects thereof, reference is had to the following description and its scope will be pointed out infth'eappended claimsp I The followingexamples will serve to" demonstrate the manner'ofpreparation of my new-thiazole and quaternary salts thereof. These examples are" not" intended, how ever; tolimit-my'ihvehtions- NH4OHl 'The oily precipitatewa's taken up in ether, dried 'with K CO and evaporated. The product was distilled under reduced pressure.

theory; The base was redistilled'in high vacuum, boiling at to 92 at 0.5 mm., after which it crystallized to longpale brown needles on'cooling. Although the most probable formula for the product" is that shown above, T

it is theoretically possible for the bromin'ation to take placejnthe position of the t'etrahyd'rothiopyranon'e'ring which would lead to theisomeric thiazole sh'own'belbvv:

However, only one product is obtained from this reaction a and regardless of, its theoretical structure, it is the new compound claimed in this invention and gives rise to the new dyes described-herein.

Example 2f-2-methyl-6,741ihydm S H-thiopyrano- (3,24) thiazole ethiodide I a f" CH- 0 5 u o-o1n iodideiwe're refluxed fol- 16 hours; The crystalline producti'was crushed under ether, filtered, washed on the filter. with" acetone, anddried'; The yield of tan crystals, The product had MQP. 152

was 13.0"gJ, 68%. with decomposition after recrystallization from absolute an l? As starting material forthe preparation of novel cyanine dyes, the 2-alkyl-6,7-dihydro-5-H-thiopyrano(3,2d)- thiazole is first converted to a quaternary salt by reacting it with an ester. such as ethyl iodide set forth hereinabove in Example II. Other examples of esters are other alkyl halides, alkyl sulfates, alkyl-p-toluene sulfonates, etc. For purposes of convenience, the quaternary salts useful in preparing the new cyanine dyes can be represented by the single formula wherein R represents an alkyl group such as methyl,

ethyl, n-propyl, isobutyl, fi-hydoxyethyl, fl-methoxyethyl, p-ethoxyethyl, fl-acetoxyethyl, p-carboxyethyl, carboxymethyl, fl-carbomethoxyethyl, p-carbethoxyethyl alkyl, etc., or an aralkyl group such as benzyl, phenyl, etc., R represents methyl, ethyl or n-propyl and X- represents an anion, e.g., chloride, bromide, iodide, benzene sulfonate, p-toluene sulfonate, methyl sulfate, ethyl sulfate, thiocyanate, perchlorate, acetate, etc.

To prepare pseudocyanine dyes from such quaternary salts, they are reacted with 2-halogenoquinoline quaternary salts in the presence of an acid binding agent such as sodium ethylate, sodium carbonate, pyridine or a strong organic base such as triethylamine, trimethylamine and N-methylpiperidine. In this connection, it has been found advantageous to employ a mixture of pyridine with astrong tertiary organic base.

Instead of 2-halogenoquinoline quaternary salts, there can be employed 2-alkylmercapto or 2-arylmercaptoquinoline quaternary salts to condense with the quaternary salts of the 2-alkyl-6,7-dihydro-5-Hthiopyrano (3,2d)thiazole in the presence of an acid binding agent.

Using 2-halogenopyridine quaternary salts instead of 2-halogenoquinoline quaternary salts, there can be prepared pyrido-cyanine dyes containing a 6,7-dihydro-5- H-thiopyrano(3,2d)thiazole nucleus.

Using 2-alkyl mercapto or 2-aryl mercapto benzothiazole or naphthothiazole salts, there can be prepared simple cyanine dyes other than pseudocyanine dyes.

To prepare symmetrical carbocyanine dyes from 2- alkyl 6,7-dihydro-5-H-thiopyrano(3,2d)thiazole quaternary salts, the quaternary salts are reacted with esters of ortho acids such as ethyl orthoform'ate, ethyl orthoacetate, ethyl orthopropionate and ethyl orthobenzoate in thepresence of pyridine or a mixture of pyridine and triethyl amine.

To prepare unsymmetrical.carbocyanine dyes ham 2-' alkyl 6,7-dihydro-5-H-thiopyrano(3,2d)thiazolequaternary salts, they are reacted with cycloammonium quaternary salts containing a fi-aryl aminovinyl group in the alpha or gamma position, i.e., in one of the so-called reactive positions in the presence of an acid binding agent, e.g., pyridine or pyridine and triethylamine.

To prepare styryl dyes from the new quaternary salts of this invention, they are condensed with p-dialkyl aminobenzaldehyde in the presence of an alkaline catalyst such as piperidine in absolute ethanol solution.

To prepare merocarbocyanine dyes from 2-alkyl-6,7- dihydro-5-H-thiopyrano(3,2d)thiazole quaternary salts, they are condensed with ketomethylene heterocyclic intermediates containing an aryl aminomethylene group in the 5-position in the presence of an acid binding agent, e.g., pyridine plus triethylamine. Examples of such ketomethylene intermediates are S-acetanilidomethylene-fiethyl rhodanine, 5acetanidomethylene-3-ethyl-1-phenyl-2- thiohydantoin, etc.

To sensitize photographic silver halide emulsions with the aforesaid dyes, they are dispersed in the emulsions such as the conventional gelatino-silver halide, e.g., gelatino-silver bromide, bromoiodide, chloride and chlorobromide. The methods of incorporating these dyes in the emulsions are simple and well known to those skilled in the art, and described .in various patents and publications. A typical method, for example, is the one described in US. Patent 2,336,843, patented December 14,

While there have been described what are at present considered to be the preferred embodiments of this invention, it'will be obvious to those skilled in the art that various changes and modifications may be made therein without departing from the invention, and it is, therefore, intended to cover all such changes and modifications as fall within the true spirit and scope of the invention.

What is claimed is:

1. The new compound, 2-alkyl-6,7-dihydro-5-H-thiopyrano(3,2d)thiazole having the general formula:

H I H: c. \N/

where R represents an alkyl radical C H and n is a positive integer selected from the group, one to three, both inclusive.

2. The new compound 2-methyl-6,7-dihydro-5-H-thiopyrano(3,2d )thiazole having the structure:

CH2.C

3. The new compound consisting of a quaternary salt of the compound described in claim 1 having the following general formula:

pyrano(3,2d)thiazole ethiodide having the structure:

5. The new compound 2-methyl-6,7-dihydro-5-H-thiopyrano(3,2d)thiazole etho-p-toluene sulfonate having the structure:- I

6. process for preparing new 2-alkyl-6,7-dihydro- S-H-thlopyrano(3,2d)thiazole bases consisting of reacting 2,4,5,6-tetrahydro-1-thio-3-pyranone with N-bromo sucv cinimide in carbon tetrachloride solution and after removal of the CC], reacting the product with a thioamide selected from the group consisting of thioacetamide, thiopropionamide and thiobutamide.

7. A process for preparing 2-methyl-6,7-dihydro-5-H- thiopyrano(3,2d)thiazole consisting of reacting 2,4,5,6- tetrahydro-l-thio-3-pyranone with N-bromo suocinirnide in carbon tetrachloride solution and, after removal of the carbon tetrachloride, reacting the product with thioacetamide in absolute ethanol solution.

8. A process for preparing quaternary salts of the folling general formula:

s s C \C/ an t H CH3 III in which R represents a member selected from the group consisting of alkyl and aralkyl groups, R represents an alkyl group and X represents an anion comprising reacting 2 alkyl-6,7-dihydro-5-H-thiopyrano(3,2d) thiazolo with a reagent selected from the group consisting of alkyl halides, aralkyl halides and esters of sulfuric acid and p-toluene sulfonic acid.

9. A process for preparing 2-methyl-6,7-dihydro-5-H- thiopyrano(3,2d)thiazole ethiodide consisting of heating 2 methyl-6,7-dihydro-5-H-thiopyrano(3,2d) thiazole with ethyl iodide.

10. A process for preparing 2-methyl-6,7-dihydro-5-H- thiopyrano(3,2d)thiazole etho-p-toluene sulfonate consisting of heating 2-rnethyl-6,7-dihydro-5-H-thiopyrano- (3,2d)thiazole with ethyl-p-toluene sulfonate.

References Cited in the file of this patent Elderfield: Heterocyclic Compounds, vol. 5, pp. 496-8, 519 (1957). 

1. THE NEW COMPOUND, 2-ALKYL-6,7-DIHYDRO-5-H-THIOPYRANO(3,2D)THIAZOLE HAVING THE GENERAL FORMULA:
 3. THE NEW COMPOUND CONSISTING OF A QUSTERNANY SALT OF THE COMPOUND DESCRIBED IN CLAIM 1 HAVING THE FOLLOWING GENERAL FORMULA: 